6. ETA Section 4-5 Flashcards
Describe the structure of a B cell receptor (BCR)
- Y-shaped with 2 identical, asymmetrical antigen-binding site
- 4 polypeptide chain
- Transmembrane region to anchor receptor in plasma memb
- At tip of Y shape, Variable region -> aa sequence varies extensively between diff B cells
In Constant region -> aa sequence vary v little
Explain primary diversification of Ig repertoire through B cell development
- Multiple variable gene segment
Germline diversity (multiple copies of V, D, J gene segments) - Combinatorial diversity
V, D, J segments selected randomly during V(D)J arrangement - Junctional diversity
During formation of junction between gene segment, recombination between segments not precise lead to junctional diversity
Different coding sequences can be created at joint through random addition of nucleotides - Multiple combination of light and heavy chain
Any heavy chain can associate with any light chain (random assortment lead to diversity)
Explain secondary diversification of Ig repertoire
- Affinity maturation
Germline DNA subjected to mutations, allowing coding for antibodies with increased affinity for binding to antigen
Hence affinity maturation is the process by which affinity of Igs produced in response to an Ag increases with repeated exposure to that Ag
Result of somatic hypermutation -> V regions undergo higher rate of mutation - Class switching
Heavy chains on constant region and heavy chain on variable can be arranged to associate with different heavy chain on constant at different times during immune response
DNA recombination between different regions called switch regions - using different constant regions create additional diversity, V region remain constant (antigen specificity remain)
Result when B cells receive cytokine signal from helper T cell
Involve deletion of intervening DNA between switch region -> cannot switch back
What is an epitope
small accessible portion of an ANTIGEN that binds to an antigen receptor
Antigen has many epitope, bind to diff receptor with diff specificity
All antigen receptors on B/T are specific to a particular epitope (as the receptors r identical)
Explain the structure of Ig G
most common circulating antibody
Produced in large qty in secondary antibody response
Is bivalent (2 identical Ag-binding site that bind 2 identical epitope)
γ gamma chain, with four human subIgG classes (lg G1, lgG2..) with heavy chains (γ1, γ2…)
Tail region of IgG binds to specific receptors on macrophage and neutrophils via (Fc receptors)
What is the genetic basis of antibody structure ?
Somatic Recombination : genes encoding variable regions of Antigen receptors are formed during lymphocyte development
Relatively limited set of germline DNA sequences brought together by enzymatic deletion of intervening sequences and then religation
Occur in developing B and T lymphocyte before Ag exposure
Occurs for both heavy and light chain genes by enzyme complex V(D)J complex
Once complete light and heavy chain genes assembled, Ig light and heavy chains synthesized, polypeptide chains assembled as Ig molecule
Antibody diversity created by recombining different gene segment to create different Variable regions